Gender differences in sleep architecture in sleep apnoea syndrome

SUMMARY  This study compared sleep architecture in women and men with sleep apnoea syndrome. Women ( n = 126) had longer sleep latencies, greater amounts of slow wave sleep, and fewer awakenings during the night than men ( n = 181), despite no differences in age, RDI (Respiratory Disturbance Index) or oxygen saturation. In a subgroup of men and women treated with nasal CPAP, gender differences generally persisted. There was no difference in the complaint of daytime sleepiness between the groups, but the women reported more fatigue during the day than the men, as well as complaining about more sleep disturbance at night. We interpret these differences in terms of known gender differences in sleep architecture and sleep complaints.     

Naltrexone improves blood gas patterns in obstructive sleep apnoea syndrome through its influence on sleep

Endogenous opiates have been shown to depress ventilation, and could therefore play a role in sleep apnoea syndrome (SAS). Hence, opiate antagonists have been used to treat SAS. The improvement they seem to give in blood-gas monitoring could derive either from a direct blocking of endorphins that inhibit respiration or else, indirectly, through an influence on sleep patterns. The present study used a double blind cross-over protocol to investigate the relationships between the effects on blood-gas and on sleep patterns of the oral opiate antagonist naltrexone in obstructive SAS. Sleep patterns and transcutaneous blood gas (tcPO2 and tcPCO2) were recorded in parallel. Control recordings, without treatment, were carried out over two nights, followed by two nights of recording after administration either of naltrexone followed by a placebo or of a placebo followed by naltrexone. The number of obstructive apnoea and hypopnoea events per hour of sleep (Apnoea-Hypopnoea Index: AHI), of hypoxic events (defined as a tcPO2 fall of at least 10, 15 or 20 mm Hg) and of hypercapnic events (defined as a tcPCO2 increase of at least 5 mm Hg) were counted. A Metabolic Suffering Index (MSI) was calculated, defined as the product of the number, duration and magnitude of hypoxic and hypercapnic events. Compared to placebo, naltrexone resulted in significant improvements in blood-gas patterns for the duration and MSI of hypoxic events and for the number, duration and MSI of hypercapnic events. Likewise, compared to placebo, naltrexone induced significant decreases in total sleep time, slow-wave sleep and rapid eye movement (REM) sleep, and, on the other hand, significant increases in total wake time and in the number of wakenings per hour of sleep (Nw h-1). Certain naltrexone-linked blood-gas improvements were closely correlated with certain of the sleep pattern changes: the decrease in number and duration of hypoxic events correlated with REM-time decrease and the decrease in number and duration of hypercapnic events correlated with the increase in Nwh-1. These findings suggest that the improvement in blood-gas patterns induced by naltrexone in SAS may be mediated by sleep pattern effects: i.e. a decrease in REM-time and an increase in intra-sleep wakening.     

The value of one hour daytime sleep recording in the diagnosis of the sleep apnoea syndrome

In this study we investigated whether the diagnosis of sleep apnoea syndrome (SAS), based on night-time polysomnography (NPSG), can be predicted or excluded by a one-hour daytime polysomnography (DPSG). The results of 306 NPSGs were compared with DPSGs, which were performed the day before. Treated patients were excluded. In the 89 patients with SAS (Apnoea index (AI)>/=5) 59 showed apnoeas during the DPSG and 30 did not. In the 217 without SAS 25 showed apnoeas daring DPSG and 192 did not. Sensitivity for detecting SAS was 66%, the specificity was 88%, the positive predictive value (PPV) 70% and the negative predictive value (NPV) 86%. For relevant SAS (AI>/=10) the NPV would be 95%. We conclude that the one-hour DPSG is not sufficient for diagnosing or excluding SAS with certainty. It can be used to make the presence of relevant SAS unlikely.     

Impairment of daytime cerebrovascular reactivity in patients with obstructive sleep apnoea syndrome

Several studies have demonstrated a clear association between snoring, sleep apnoea and increased risk of stroke. However, the possible role of sleep apnoea in the pathophysiogenetic mechanisms of cerebrovascular disease is still unknown. Our aim in this study was to investigate cerebral haemodynamic changes during the waking state in eight patients with sleep apnoea syndrome (OSAS) by means of transcranial Doppler (TCD). In particular, we studied cerebral vascular reactivity (CVR) to hypercapnia calculated by means of the breath holding index (BHI). The investigation was performed in the early morning, soon after awakening, and in the late afternoon. Data were compared with those of eight healthy subjects matched for age and vascular risk factors. OSAS patients showed significantly lower BHI values with respect to controls both in the morning (0.56 vs. 1.36; P < 0.0001) and in the afternoon (1.12 vs. 1.53; P < 0.0001). In patients, BHI values in the afternoon were significantly higher than in the morning ( P < 0.0001). These data demonstrate a diminished vasodilator reserve in OSAS patients, particularly evident in the morning. This reduction of the possibility of cerebral vessels to adapt functionally in response to stimulation could be linked to hyposensitivity of cerebrovascular chemoreceptors after the continuous stress caused by nocturnal hypercapnia.     

Reduced cerebral blood flow during wakefulness in obstructive sleep apnea-hypopnea syndrome

STUDY OBJECTIVES: To investigate changes in regional cerebral blood flow (rCBF) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). DESIGN: We compared the 99mTc-ethylcysteinate dimer (ECD) single photon emission computed tomography (SPECT) images of patients with OSAHS with those of age- and sex-matched healthy volunteers. SETTING: University hospital. PATIENTS AND PARTICIPANTS: Twenty-seven patients with severe OSAHS and 27 healthy volunteers underwent 99mTc-ECD brain SPECT studies. INTERVENTION: For statistical parametric mapping analysis, all SPECT images were spatially normalized to the standard SPECT template and then smoothed using a 14-mm full-width at half-maximum Gaussian kernel. The Student t test was used for the statistical analysis. MEASUREMENTS AND RESULTS: The mean age of patients and subjects was 44.3 years (range 31-58). All patients underwent overnight polysomnography. The mean apnea-hypopnea index of patients was 60.4 +/- 17.6 per hour (range 33 -104), indicating severe OSAHS. All patients snored heavily and had daytime sleepiness (mean Epworth Sleepiness Scale score, 10.7 +/- 3.7, range 6-12). Statistical parametric mapping analysis showed that rCBF in patients with OSAHS was significantly reduced in bilateral parahippocampal gyri and in the right lingual gyrus, as compared with that of healthy volunteers (P < 0.05 with false discovery rate correction). Moreover, apnea-hypopnea indexes of patients were negatively correlated with rCBF in the right pericentral gyrus and right cuneus at uncorrected P < 0.001. CONCLUSIONS: Our results show the altered rCBF pattern in bilateral parahippocampal gyri, right lingual gyrus, pericentral gyrus, and cuneus in patients with severe OSAHS. These findings may partly explain the deficit in memory, spatial learning, executive function, and attention, which are frequently found in patients with OSAHS.     

Microarousals in patients with sleep apnoea/hypopnoea syndrome

SUMMARY Upper airway obstructions during sleep cause recurrent brief awakenings or microarousals. Standard criteria exist for sleep and respiratory event scoring, however, there are different definitions currently used to score microarousals. We therefore compared three definitions of microarousal (ranging from 1.5-3 s in duration) and one of awakening (> 15 s). We examined their occurrence at the termination of apnoeas and hypopnoeas and their correlation with daytime sleepiness in patients with sleep apnoea/hypopnoea syndrome (SAHS). Sixty-three patients (aged 49, SD 10) had overnight polysomnography, multiple sleep latency tests (MSLT) and Epworth Sleepiness Scales (ESS). There were significantly more microarousals by any definition than there were awakenings (P<0.001) and there were more 1.5 s than 3 s microarousals (P<0.001). Significantly more apnoeas and hypopnoeas were terminated by 1.5 s microarousals (83% and 81%) than by 3 s microarousals (75%) (all P<0.001). Apnoea/hypopnoea index (AHI) correlated significantly with objective daytime sleepiness (p = -0.30, P<0.01). There were weakly significant relationships between all three microarousal definitions (-0.24<P< -0.22, 0.03<P<0.04) and objective daytime sleepiness. None of the arousal definitions correlated with Epworth Sleepiness Scales scores. These results suggest that although 1.5 s microarousals are found at the end of more respiratory events, relationships between 3 and 1.5 s definitions, and daytime sleepiness are similar. This indicates that any of the three microarousal definitions can be used for visual assessment of sleep fragmentation.     

Cortico-motoneurone excitability in patients with obstructive sleep apnoea

A disordered neuromotor control of pharynx muscles may play a role in the genesis of obstructive sleep apnoea syndrome (OSAS). This raises the possibility of a dysfunction of projections descending from the cortex to segmental nuclei. With single pulse transcranial magnetic stimulation (TMS) we studied the physiology of the corticospinal projection to hand muscles in seven OSAS patients. At first, we compared them with nine age- and sex-matched normal controls in the wake state. The only abnormality was a lengthening of the central silent period (P < 0.001). This supports a steady imbalance of motor cortical interneurone activities towards a state of enhanced inhibition. Then we looked at changes of the motor-evoked potential (MEP) size and latency, according to whether patients were awake, or in a non-rapid eye movement (REM) 2 sleep stage, or during a typical apnoea. During non-REM 2 sleep, the average MEP amplitude was significantly (P < 0.05) smaller than in the awake state. The MEP latency was, in turn, significantly longer (P < 0.05). During apnoeas, the MEP size decreased, and the latency increased further (P < 0.05), indicating an extra depression of the cortico-motoneuronal activity. All TMS changes were detected outside the pharyngeal district, suggesting a widespread dysfunction of the cortico-motoneuronal system in the OSAS, which is more evident during apnoeas.     

Sleep-related sweating in obstructive sleep apnoea: association with sleep stages and blood pressure

The aim of this study was to investigate sleep-related sweating as a symptom of obstructive sleep apnoea (OSA). Fifteen otherwise healthy male non-smoking patients with untreated moderate-to-severe OSA underwent polysomnography, including measurements of skin and core body temperature and electrodermal activity (EDA) as an objective indicator of sweating. Evening and morning blood pressure was measured as well as catecholamines in nocturnal urine. All measurements were repeated after 3 months on successful continuous positive airway pressure (CPAP) treatment. The untreated OSA subjects had a mean (±SD) apnoea–hypopnoea index of 45.3 ± 3.9 and a mean EDA index during sleep of 131.9 ± 22.4 events per hour. Patients with higher EDA indices had higher systolic blood pressure in the evening and morning ( P  = 0.001 and 0.006) and lower rapid eye movement (REM) sleep percentage ( P  = 0.003). The EDA index decreased significantly to 78.5 ± 17.7 in the patients on CPAP treatment ( P  = 0.04). The decrease correlated with lower evening systolic and diastolic blood pressure ( P  = 0.05 and 0.006) and an increase in REM% ( P  = 0.02). No relationship was observed between EDA and skin or core body temperature, or to catecholamine levels in urine. OSA patients who experience sleep-related sweating may have increased blood pressure and decreased REM sleep compared with other OSA patients. CPAP treatment appears to lower blood pressure and increase REM sleep to a higher extent in these patients compared with other OSA patients.     

Determinants of circadian blood pressure rhythm and blood pressure variability in obstructive sleep apnoea

SUMMARY  The prevalence of hypertension in patients with obstructive sleep apnoea (OSA) is high and blood pressure profile is characterized by nocturnal blood pressure (BP) elevation and increased nocturnal BP variability. Ambulatory 24-hour-biood pressure monitoring (ABPM) is a valid, non-invasive method to describe circadian BP variation. Circadian BP profile and nocturnal BP variability were related to OSA severity (apnoea-hypopnoea index, mean low O₂), age and body mass index (BMI) in 73 patients with OSA. Prevalence of hypertension was 75%, and in 59% BMI was greater than 30 kg m^-2. A nocturnal decline of at least 10% from daytime mean BP values (night/day BP ratio <0.9; dipper) was found in only 25% of hypertensive patients and 39% of normotensive patients. Comparison between dippers and non-dippers showed significant differences in apnoea severity (apnoea-hypopnoea index 32 + 19 vs. 50 + 23/h, P <0.01; mean low O₂ 84.5 + 4 vs. 80.2 + 5.8%, P< 0.01) but not for age and BMI. In multiple regression analyses with age, body mass index, apnoea-hypopnoea index and mean low O₂ as independent and BP ratios and BP variability as dependent variables, sleep apnoea severity was the only independent predictor for circadian BP rhythm and nocturnal BP variability. The results presented here suggest that independent of age and obesity the severity of sleep apnoea is an important determinant of circadian BP variation and nocturnal BP variability.     

Under reporting of sleepiness and driving impairment in patients with sleep apnoea/hypopnoea syndrome

SUMMARY Under reporting of symptoms by patients with sleep apnoeal/hypopnoea syndrome (SAHS) has been reported anecdotally, but investigation of the prevalence or determinants of this is limited. To assess this, repeated ratings in 99 patients with sleep apnoea/hypopnoea syndrome of pre-treatment Epworth sleepiness score, unintended napping, driving impairment and mood were obtained, first at presentation and then after treatment with continuous positive airway pressure (CPAP) therapy of median 22 (range 2-70) weeks duration. Median Epworth score for pre-treatment sleepiness rose from 12 (range 0-24) initially to 14 (range 5-24) retrospectively (P<0.0001). More patients initially under-rated Epworth score (67%) than over-rated (29%; P0.001). ‘False negative’ cases with an initially ‘normal’ (≤ 10) and retrospectively ‘sleepy’ (≥ 11) Epworth score comprised 24% of all patients and 62% of initially ‘normal’ scorers. Unintended napping behaviour also was rated as significantly more severe on retrospective assessment (P<0.001). Driving impairment due to sleepiness was initially reported by 23% of all drivers and retrospectively by 37% (P=0.01), with 25% of initial deniers retrospectively admitting compromised driving ability before continuous positive airway pressure. No polysomnographic predictors of symptom under reporting were found (P 0.1). These results suggest a high prevalence of symptom minimization before treatment in patients with sleep apnoea/hypopnoea syndrome.     

Influence of obstructive sleep apnoea on circadian blood pressure profile

SUMMARY  A high prevalence of systemic hypertension in obstructive sleep apnoea (OSA) has been described but data on circadian blood pressure (BP) profile are limited and give inconsistent results. The present study examines 24-h BP in 106 patients referred because of loud snoring or excessive daytime sleepiness in combination with snoring. Patients were classified as OSA ( n = 62) or habitual snorers (HS) ( n = 44). Respiratory disturbance index (RDI) in OSA was 47 ± 24 vs. 2 ± 2 in HS. Mean age and body mass index in OSA was significantly higher.
BP was measured non-invasively at 15-min intervals during a 24-h period. Daytime and night-time BP was higher in OSA compared to HS. BP night/day ratio in OSA was 0.92 ± 0.07 vs. 0.86 ± 0.06 in HS ( P < 0.05). To investigate the influence of variables other than breathing abnormalities during sleep on our results we compared BP profiles of 25 OSA and 25 HS matched for sex, age and body weight. Again differences in daytime and night-time BP and BP night/day ratio were significant. Using a value of at least 10% fall in nocturnal BP to describe a regular BP profile (dipper) 68% of OSA were classified as non-dippers vs. 24% of HS.
Influence of short-term (2–4 days) nCPAP therapy on circadian BP profile was investigated in 34 patients with OSA. Systolic and diastolic nocturnal (but not daytime) BP was significantly reduced. The percentage of non-dippers was 79% before and 50% after treatment. In conclusion results of this study indicate a causal link between OSA and abnormal circadian BP profile.     

Prevalence of papilloedema in patients with sleep apnoea syndrome: a prospective study

The association of papilloedema (PO) with respiratory diseases and especially obstructive sleep apnoea (OSA) syndrome has been emphasised in many reports. The pathophysiology could rely on the episodic increase of intracranial pressure related to apnoeic episodes during night sleep. Nevertheless, prevalence of papilloedema in patient with OSA syndrome remains unknown. As this information could improve diagnosis and therapeutic strategies, the aim of the present study was to investigate the prevalence of PO in an OSA syndrome population. From 95 successive, recently diagnosed OSA patients, 35 answered a questionnaire about visual symptoms and underwent fundoscopic examination. Visual symptoms suggestive of PO were present in 40% of the patients, but none had PO. As a conclusion, PO does not seem to be frequently associated with OSA syndrome and systematic screening of PO in these patients does not seem to be warranted. Nevertheless, patients with visual complaints evocative of papilloedema should have their eye fundus checked since the association between OSA and PO exists. Further studies, including more patients, might be useful to establish which patients are at particular risk for this complication.     

Obstructive sleep apnoea syndrome in hereditarygelsolin-related amyloidosis

Gelsolin-related amyloidosis (AGel amyloidosis) is a rare autosomal dominant disorder, reported worldwide in kindreds carrying a G654A or G654T gelsolin gene mutation. The main clinical signs are cutis laxa, cranial and peripheral neuropathy, and corneal lattice dystrophy but heavy intermittent snoring also occurs. To evaluate whether sleep apnoea is present we performed nocturnal sleep recordings, cephalometric and spirometric analyses and multiple sleep latency tests (MSLT) in five snoring patients with a G654A gelsolin gene mutation. Four patients had obstructive sleep apnoea syndrome (OSAS) with redundant oropharyngeal and hypopharyngeal soft tissues, macroglossia and cranial neuromuscular dysfunction. The fifth patient had hypersomnia without obstructive sleep apnoea. Nasal continuous positive airway pressure (CPAP) was an effective treatment. This study presents the first evidence in favour of an association between AGel amyloidosis and OSAS, but further studies are needed to define the prevalence of OSAS and the pathogenetic roles of amyloid and variant gelsolin in its evolution.     

The severity of obstructive sleep apnoea is associated with insulin resistance

Oral glucose tolerance tests (OGTT) were performed on eighteen patients with suspected obstructive sleep apnoea who also completed a whole-night polygraphic recording with oximetry. Insulin resistance indices (IRI) were calculated as the product of areas under glucose and insulin curves. In the resulting multiple regression analysis the dependent variable was IRI and the independent variables were age, body mass index (BMI) and the number of nocturnal hypoxic episodes with over 4% desaturation per hour (ODI4). ODI4 was between 4.6 and 70 (median 22.3); IRI ranged from 2.20 to 33.55 (median 7.50). In the regression model the coefficient of determination (R2) for IRI was 0.441 (F-ratio = 3.681, P = 0.038). The strongest determinant of IRI was ODI4 and the regression coefficient of BMI was not significantly different from zero even when possible outliers were excluded. It was found that insulin resistance is related to the severity of sleep anoea. This may be due to a hypoxia-induced hormonal stress reaction which decreases tissue insulin sensitivity. Since upper body obesity is associated with both insulin resistance and sleep apnoea, the distribution of fat should be taken into account in future studies.